A new study shows that embryonic nerve cells can functionally integrate into local neural networks when transplanted into damaged areas of the visual cortex of adult mice.
(Image caption: Neuronal transplants (blue) connect with host neurons (yellow) in the adult mouse brain in a highly specific manner, rebuilding neural networks lost upon injury. Credit: Sofia Grade, LMU/Helmholtz Zentrum München)
When it comes to recovering from insult, the adult human brain has
very little ability to compensate for nerve-cell loss. Biomedical
researchers and clinicians are therefore exploring the possibility of
using transplanted nerve cells to replace neurons that have been
irreparably damaged as a result of trauma or disease. Previous studies
have suggested there is potential to remedy at least some of the
clinical symptoms resulting from acquired brain disease through the
transplantation of fetal nerve cells into damaged neuronal networks.
However, it is not clear whether transplanted intact neurons can be
sufficiently integrated to result in restored function of the lesioned
network. Now researchers based at LMU Munich, the Max Planck Institute
for Neurobiology in Martinsried and the Helmholtz Zentrum München have
demonstrated that, in mice, transplanted embryonic nerve cells can
indeed be incorporated into an existing network in such a way that they
correctly carry out the tasks performed by the damaged cells originally
found in that position. Such work is of importance in the potential
treatment of all acquired brain disease including neurodegenerative
illnesses such as Alzheimer‘s or Parkinson’s disease, as well as strokes
and trauma, given each disease state leads to the large-scale,
irreversible loss of nerve cells and the acquisition of a what is
usually a lifelong neurological deficit for the affected person.
In the study published in Nature, researchers of the Ludwig
Maximilians University Munich, the Max Planck Institute of Neurobiology,
and the Helmholtz Zentrum München have specifically asked whether
transplanted embryonic nerve cells can functionally integrate into the
visual cortex of adult mice. “This region of the brain is ideal for such
experiments,” says Magdalena Götz,
joint leader of the study together with Mark Hübener. Hübener is a
specialist in the structure and function of the mouse visual cortex in
Professor Tobias Bonhoeffer’s Department (Synapses – Circuits –
Plasticity) at the MPI for Neurobiology. As Hübener explains, “we know
so much about the functions of the nerve cells in this region and the
connections between them that we can readily assess whether the
implanted nerve cells actually perform the tasks normally carried out by
the network.” In their experiments, the team transplanted embryonic
nerve cells from the cerebral cortex into lesioned areas of the visual
cortex of adult mice. Over the course of the following weeks and months,
they monitored the behavior of the implanted, immature neurons by means
of two-photon microscopy to ascertain whether they differentiated into
so-called pyramidal cells, a cell type normally found in the area of
interest. “The very fact that the cells survived and continued to
develop was very encouraging,” Hübener remarks. “But things got really
exciting when we took a closer look at the electrical activity of the
transplanted cells.” In their joint study, PhD student Susanne Falkner
and Postdoc Sofia Grade were able to show that the new cells formed the
synaptic connections that neurons in their position in the network would
normally make, and that they responded to visual stimuli.
The team then went on to characterize, for the first time, the
broader pattern of connections made by the transplanted neurons.
Astonishingly, they found that pyramidal cells derived from the
transplanted immature neurons formed functional connections with the
appropriate nerve cells all over the brain. In other words, they
received precisely the same inputs as their predecessors in the network.
In addition, they were able to process that information and pass it on
to the downstream neurons which had also differentiated in the correct
manner. “These findings demonstrate that the implanted nerve cells have
integrated with high precision into a neuronal network into which, under
normal conditions, new nerve cells would never have been incorporated,”
explains Götz, whose work at the Helmholtz Zentrum and at LMU focuses
on finding ways to replace lost neurons in the central nervous system.
The new study reveals that immature neurons are capable of correctly
responding to differentiation signals in the adult mammalian brain and
can close functional gaps in an existing neural network.
Toshinori sat on the living room couch, thumbing through a novel Ectoplasm suggested. Soft banter from his students drifted from the kitchen and dining area where studying was in full swing. Occasionally, a student came to him for help on their assignments. It brought a smile to Toshinori’s face. The moments were brief, but he was teaching again.
His ears flicked and skewed the glasses perched on his nose.
, he clicked his tongue, setting his book aside to fix the large, round, wire-frame glasses. During his last exam with Recovery Girl, she checked his eyes for any changes the night vision quirk may have caused.
“You’ll need reading glasses,”
“Honestly, you’ve needed them for a while. I’ll have a pair made for you before you start getting migraines.”
Should have known, given her fashion sense…
Toshinori chuckled, remembering the look on his face when he saw himself wearing them for the first time. He gaped at himself in the mirror, but the kids loved them and insisted they were perfect.
With his glasses righted, he returned to his book and his dexterity exercises.
Tail lifting and curling, Toshinori carefully moved a small pillow from the floor and set in on the pillow pyramid he’d stacked at his side. It was Ojiro’s idea to get a better feel for his tail, and young Yaoyorozu was kind enough to create a number of different shaped pillows for him.
Toshinori was shocked to find the tip of his tail was incredibly flexible and, with practice, almost as useful as a third hand. With a sweep of his tail he knocked the neat pile to the ground and began again.
Halfway through the next pyramid, Toshinori’s cell phone buzzed in his pocket. He pulled it out, grinning at the name on the screen.
“Naomasa! Hello,” he answered, scooping up the remaining pillows on the floor and depositing them on the couch. Standing, he bashfully waved at the few curious students looking his way and excused himself, “How are you?”
Pyramidal neurons and their dendrites from a mouse brain
Named for their triangular cell bodies, pyramidal neurons reside in the brain and act as the main conduit of information flow, passing on electrical signals from one area of the brain to the next. Pyramidal neurons are known for their many branches of dendrites, the inputs of a neuron that–when efficiently stimulated–trigger a neuron to fire a signal to other neurons. Dendritic branching allows a single neuron to communicate with thousands of others within a network, all within a fraction of a second.
Image by Dr. Alexandre Moreau, University College London.